Treatment selection for esophageal cancer: evaluation from a nationwide database

Abstract

Background

Most elderly patients poorly tolerate the standard treatment for esophageal cancer; however, little information is available regarding the appropriateness of non-standard esophageal cancer treatments for those patients. This study aims to analyze the treatment costs and completion rates of patients undergoing a real-world treatment for esophageal cancer to elucidate the treatment selection and its quality.

Materials and methods

We analyzed treatment costs and completion rates for patients with esophageal cancer and analyzed these data relative to patient age and center volumes. Patients with esophageal cancer [UICC, TMN, Clinical stage II/III (excluding T4)] who were diagnosed in 2013 were analyzed. Patients were classified into five groups defined as follows: surgical therapy, chemotherapy, concurrent chemoradiotherapy (CCRT), modified concurrent chemoradiotherapy (mCRT), and radiotherapy (RT).

Results

Mean and median age of patients who received surgery and CCRT were comparable; however, patients who underwent mCRT and RT tended to be older. Medical costs associated with surgery were higher than costs associated with other non-surgical treatments. Cost and completion rate of chemoradiotherapy did not differ between CCRT and mCRT; however, both had higher completion rates compared to that of RT. Surgical expenses tended to be the highest in low-volume centers and the lowest in high-volume centers.

Conclusion

Treatment of esophageal cancer at high-volume centers seems well balanced compared with medium- to low-volume centers. mCRT was widely performed and comparable in medical cost to CCRT, although additional clinical impacts were unclear.

Conflicting intentions: rectifying the consistency requirements

Abstract

Many philosophers are convinced that rationality dictates that one's overall set of intentions be consistent. The starting point and inspiration for our study is Bratman's planning theory of intentions. According to this theory, one needs to appeal to the fulfilment of characteristic planning roles to justify norms that apply to our intentions. Our main objective is to demonstrate that one can be rational despite having mutually inconsistent intentions. Conversely, it is also shown that one can be irrational despite having a consistent overall set of intentions. To overcome this paradox, we argue that it is essential for a successful planning system that one's intentions are practically consistent rather than being consistent or applying an aggregation procedure. Our arguments suggest that a new type of norm is needed: whereas the consistency requirement focuses on rendering the contents of one's intentions consistent, our new practical consistency requirement demands that one's intentions be able to simultaneously and unconditionally guide one's action. We observe that for intentions that conform to the 'own-action condition', the practical consistency requirement is equivalent to the traditional consistency requirement. This implies that the consistency requirement only needs to be amended in scenarios of choice under uncertainty.

Responsibility for forgetting

Abstract

In this paper, we focus on whether and to what extent we judge that people are responsible for the consequences of their forgetfulness. We ran a series of behavioral studies to measure judgments of responsibility for the consequences of forgetfulness. Our results show that we are disposed to hold others responsible for some of their forgetfulness. The level of stress that the forgetful agent is under modulates judgments of responsibility, though the level of care that the agent exhibits toward performing the forgotten action does not. We argue that this result has important implications for a long-running debate about the nature of responsible agency.

Bier spots treated with intense pulsed light

Adsorptive removal of organics from aqueous phase by acid-activated coal fly ash: preparation, adsorption, and Fenton regenerative valorization of “spent” adsorbent

Abstract

Raw coal fly ash was activated to an adsorbent by sulfuric acid impregnation. The activation condition, the adsorption capacity, and the regenerative valorization of the adsorbent were studied. The results show that the optimal preparation conditions of the adsorbent are [H₂SO₄] = 1 mol L⁻¹, activation time = 30 min, the ratio of coal fly ash to acid = 1:20 (g:mL), calcination temperature = 100 °C. The adsorption of p-nitrophenol on the adsorbent accords with the pseudo-second-order kinetic equation and the adsorption rate constant is 0.089 g mg⁻¹ min⁻¹. The adsorption on this adsorbent can be considered enough after 35 min, when the corresponding adsorption capacity is 1.07 mg g⁻¹ (85.6% of p-nitrophenol removal). Compared with raw coal fly ash, the adsorbent has a stable adsorption performance at low pH range (pH = 1–6) and the adsorption of p-nitrophenol is an exothermic process. Ninety minutes is required for the regenerative valorization of saturated adsorbent by Fenton process. The regenerative valorization for this saturated adsorbent can reach 89% under the optimal proposed conditions (30 °C, pH = 3, [H₂O₂] = 5.0 mmol L⁻¹, [Fe²⁺] = 5.5 mmol L⁻¹). Within 15 experimental runs, the adsorbent has a better and better stability with the increase of experimental runs. Finally, the mechanism of activating coal fly ash is proposed, being verified by the results of the SEM and BET test.

The environmental Kuznets curve in the presence of corruption in developing countries

Abstract

Environmental degradation is at an alarming level in developing economies. The present paper examines the direct and indirect impacts of corruption on environmental deterioration using the panel data of 64 developing countries. Adopting the generalized method of moments (GMM) technique, the paper finds evidence that corruption exhibits a positive impact on pollution. Subsequently, there is also evidence indicating that the level of pollution tends to be higher in countries with a higher level of corruption, eliminating the effectiveness of income effect on environmental preservation. These results also suggest that environmental degradation is monotonically increasing with higher corruption and invalidate the presence of the EKC. Hence, a policy focuses that an anti-corruption particularly in the environmental and natural resources sector needs to be emphasized and enforced in order to reduce or possibly to totally eliminate the rent for corruption.

Toxicological study of the degradation products of antineoplastic agent etoposide in commercial formulation treated by heterogeneous photocatalysis using SrSnO 3

Abstract

Etoposide is an antineoplastic agent used for treating lung cancer, testicular cancer, breast cancer, pediatric cancers, and lymphomas. It is a pollutant due to its mutagenic and carcinogenic potential. Disposal of waste from this drug is still insufficiently safe, and there is no appropriate waste treatment. Therefore, it is important to use advanced oxidative processes (AOPs) for the treatment and disposal of medicines like this. The use of strontium stannate (SrSnO₃) as a catalyst in heterogeneous photocatalysis reactions has emerged as an alternative for the removal of organic pollutants. In our study, SrSnO₃ was synthesized by the combustion method and characterized by X-ray diffraction (XRD), Raman, UV-Vis, and scanning electron microscopy (SEM) techniques, obtaining a surface area of 3.28 m² g⁻¹ with cubic and well-organized crystallinity and a band gap of 4.06 eV. The experimental conditions optimized for degradation of an etoposide solution (0.4 mg L⁻¹) were pH 5 and catalyst concentration of 1 g L⁻¹. The results showed that the degradation processes using SrSnO₃ combined with H₂O₂ (0.338 mol L⁻¹) obtained total organic carbon removal from the etoposide solution, 97.98% (± 4.03 × 10⁻³), compared with TiO₂, which obtained a mineralization rate of 72.41% (± 6.95 × 10–3). After photodegradation, the degraded solution showed no toxicity to zebrafish embryos through embryotoxicity test (OECD, 236), and no genotoxicity using comet assay and micronucleus test.

Study of the efficacy of carboxytherapy in alopecia

Summary

Background

Management of alopecia areata (AA) and androgenetic alopecia (AGA) is often challenging. The use of carboxytherapy may be a novel therapeutic option for such cases.

Objective

To evaluate the clinical efficacy and safety of carboxytherapy in alopecia areata and androgenetic alopecia.

Patients and methods

This study was conducted on 80 patients with alopecia divided into two groups; Group I included 40 AA patients (Group IA received carboxytherapy and Group IB control received placebo), and Group II included 40 AGA patients (Group IIA received carboxytherapy and Group IIB control received placebo), and followed up monthly for 3 months. They were evaluated clinically (by assessment of Severity of Alopecia Tool (SALT) score in group I, and Sinclair scale and Norwood-Hamilton scale in group II), by dermoscopy and digital dermoscopy at each visit.

Results

Group IA patients showed significant clinical improvement in SALT score and dermoscopic improvement after carboxytherapy and at the end of follow-up period with significant reduction in dystrophic hair, black dots, yellow dots, and tapered hair coinciding with significant emergence of regrowing hair. Group IIA patients showed significant clinical and dermoscopic improvement after carboxytherapy with significant increase in hair density measured by digital dermoscopy. However, regression of these results was observed during the follow-up period but was still significantly better than before treatment. There were statistically significant improvements in clinical score, global assessments, dermoscopic, and digital dermoscopic findings in both group IA and group IIA received carboxytherapy in comparison with group IB and group IIB received placebo injections, respectively.

Conclusion

Carboxytherapy seems to be a promising therapeutic option for patchy AA and could be helpful as an adjuvant therapy of AGA but more than 6 sessions are required and adjuvants are recommended for maintenance of the results.

Safety assessment, biological effects, and mechanisms of Myrica rubra fruit extract for anti-melanogenesis, anti-oxidation, and free radical scavenging abilities on melanoma cells

Summary

Objective

Currently, the cosmetic and medical industries are paying considerable attention to solve or prevent skin damage or diseases, such as hyperpigmentation and oxidation and free radical damage. In this study, the effective compounds in Myrica rubra fruit were extracted and studied the biological effects of these M. rubra fruit extracts.

Methods

In this study, we extracted M. rubra fruit using solutions with various ratios of water to ethanol (100:0, 50:50, 5:95) and studied the anti-melanogenesis, anti-oxidation and radical scavenging effects of these M. rubra fruit extracts on two melanoma cell lines: mouse melanoma (B16-F0) and human melanoma (A2058). The cytotoxicity, melanin synthesis, mushroom and cellular tyrosinase activities, enzyme kinetics, melanogenesis-related gene expression, melanogenesis-related protein secretion, radical DPPH scavenging activity and ROS inhibition after treatment with M. rubra fruit extracts were determined.

Results

The results showed that the water extract of M. rubra fruit was less cytotoxic to the melanoma cell lines, effectively inhibited melanin synthesis and tyrosinase activity and down-regulated the gene expression and protein secretion of MITF and TRP-1. In addition, the M. rubra fruit extracts also showed the abilities to scavenge DPPH free radicals and suppress ROS production. Finally, the effective compounds in the water extract were Myricetin-O-deoxyhexoside, Quercetin-O-deoxyhexoside, and Kaempferol-O-hexoside determined by LC/MS/MS assay.

Conclusion

Overall, the water extract of M. rubra fruit is a safe and effective melanin inhibitor and anti-oxidant and can be applied widely in the fields of cosmetics and medicine.

Vitamin D levels in acne vulgaris patients treated with oral isotretinoin

Summary

Background/Objectives

Acne vulgaris is a common inflammatory skin disease. Vitamin D deficiency plays a role in many inflammatory skin diseases. It may play a role in pathogenesis of acne vulgaris. This study aimed to assess serum levels of 25 hydroxy vitamin D in patients with acne vulgaris before and after treatment with isotretinoin and its relation with acne vulgaris severity.

Methods

Ninety patients with acne vulgaris and 60 age-sex matched healthy subject as controls have been recruited in this study. Patients were treated with 0.75 mg/kg/d isotretinoin for 3 months. Serum level of 25 hydroxy vitamin D has been measured at baseline and after treatment.

Results

Serum levels of 25 hydroxy vitamin D were significantly higher in patients with acne vulgaris than healthy controls (P = .001). There was a significant inverse relation between level of 25 hydroxy vitamin D and severity of acne vulgaris before treatment (P = .001). Serum levels of 25 hydroxy vitamin D were significantly increased after isotretinoin treatment in patients with acne vulgaris (P = .001).

Conclusion

This study concluded that vitamin D may play a potential role in pathogenesis of acne vulgaris or acne vulgaris may have a negative effect on vitamin D synthesis. Further studies are needed to confirm these potential relations.

Comparative virulence of Candida auris with Candida haemulonii, Candida glabrata and Candida albicans in a murine model

Summary

The incidence of invasive fungal infections (IFIs) caused by uncommon Candida species with diverse virulence and susceptibility profiles has increased in recent years. Due to scarce clinical and experimental data on the pathogenicity of Candida auris, the aim of this study was to evaluate and compare the virulence of two rare clinically relevant species, C. auris and Candida haemulonii with Candida glabrata and Candida albicans in an immunocompetent murine model of disseminated infection. Immunocompetent ICR female mice were infected with three inoculum sizes (1×10⁵, 1×10⁶ and 1×10⁷ CFU/mouse) of two C. auris strains and one isolate of C. haemulonii, C. glabrata and C. albicans. Tissue burden on days 5 and 10 post challenge and mortality rate were used as virulence markers. A high virulence was found for C. albicans, followed by C. auris, C. glabrata and C. haemulonii, respectively. C. albicans showed high virulence with a medium survival time of 9.5 days for mice infected with 1×10⁷ CFU/mouse. For inocula at 1×10⁶ and 1×10⁷ CFU/mouse, there were significant differences in fungal burden at day 10 between C. albicans, C. auris and C. glabrata isolates compared with C. haemulonii (P <0.0001). Overall, no significant differences between C. albicans with C. auris and C. glabrata were observed in mice infected with three different inocula (P >0.05). In general, the highest fungal load of all isolates was detected in kidney followed by spleen, liver and lung tested with three different inocula on the two different experimental days. Histopathological examination revealed the abundant presence of yeast cells with pseudohyphae for C. albicans and only yeast cells for C. auris, C. glabrata and C. haemulonii, in all the kidney tissue samples. In conclusion, C. albicans is a highly virulent opportunistic fungus, as the clinical and experimental data demonstrate, and also our results demonstrate a low virulence of C. haemulonii in immunocompetent animals. Altogether, this study highlights the pathogenic potential of C. auris.

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Table of Contents

Dermoscopy of eccrine angiomatous hamartoma: The popcorn pattern

A 21-year-old woman presented with a congenital red-yellow, velvety plaque on the right side of the neck (Fig 1). She complained of mild pruritus and excessive sweating on that area.

Lichen planopilaris associated with pembrolizumab in a patient with metastatic melanoma

Pembrolizumab, a programmed cell death receptor 1 (PD-1) inhibitor, has been used effectively for treatment of metastatic melanoma.1 Reported cutaneous adverse events ascribed to PD-1 inhibitors include lichenoid reactions such as lichen planus of the skin and oral mucosa, lichen planus pemphigoides, and lichenoid drug eruptions, as well as alopecia areata and vitiligo.2-5 We present a patient with metastatic melanoma who had lichen planopilaris (LPP) after receiving pembrolizumab. We find no previous report in the literature of LPP in association with PD-1 inhibitors.

Editorial Board

Journal Based CME Instructions and Information

Dermoscopy of pediculosis pubis

A 62-year-old man presented to our department because of pubic pruritus for 1 week, claiming it started after wearing a new pair of briefs. Cutaneous examination found small, yellowish-brown moving flecks attached to the hair in the pubic region (Fig 1).

Successful treatment of juvenile pityriasis rubra pilaris with ustekinumab in a 7-year-old girl

Pityriasis rubra pilaris (PRP) is an uncommon inflammatory dermatosis characterized by erythematous salmon-colored plaques with islands of sparing and palmoplantar hyperkeratosis. The etiology of PRP is not well understood.1 Histopathologic features of PRP are variable but presents with some similarities to psoriasis.1,2 PRP is classified into 5 subgroups, with groups III (classical juvenile), IV (circumscribed juvenile), and V (atypical juvenile) affecting the pediatric population. These subtypes occur in approximately 10%, 25%, and 5% of PRP patients, respectively.

Ulcerative livedoid vasculopathy responding to clopidogrel

Livedoid vasculopathy (LV) is a thrombotic, noninflammatory disorder that typically affects the lower extremities. Treatments for LV are widely varied and can be difficult to obtain because of high cost or lack of availability. We present a case of LV with ulcers in an adult woman successfully treated with clopidogrel, a widely available antiplatelet agent. Our case suggests that clopidogrel can be an effective and accessible treatment option for ulcerative LV.

Digital metastasis of tongue squamous cell carcinoma

Nail disorders are common complications in oncologic patients who have received chemotherapy.1-4 The all-grade incidence of nail changes with paclitaxel treatment has been reported to be 43.7%.3 Nail characteristics can be divided into anatomic sites—nail matrix (Beau's line, onychomadesis), nail bed (onycholysis, pigmentation changes), and nail fold (paronychia, pyogenic granuloma). This study reports a patient with advanced squamous cell carcinoma of the tongue who had nail changes on the left index finger after treatment with taxane chemotherapy and an epidermal growth factor receptor inhibitor.

A pink and purple plaque

A 79-year-old man presented for evaluation of a slowly growing pink scaly plaque on his right knee. An eccentric violaceous papule was noted on its medial edge (Fig 1).

The relevance of a suppressor of fused (SUFU) mutation in the diagnosis and treatment of Gorlin syndrome

Nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome (GS), is an aberrant activation of the sonic hedgehog pathway (Hh). GS was first described in the literature in 1894 and the Hh pathway's role in its development was discovered thereafter.1 The Hh pathway regulates cell growth and development of the integumentary, central nervous, and musculoskeletal systems, where its overactivation causes abnormalities. In GS, this manifests as, among other clinical sequela, numerous basal cell carcinomas (BCC) that vary in quantity from a few to several thousand.

Juvenile interleukin-36 receptor antagonist deficiency (DITRA) with c.80T>C (p.Leu27Pro) mutation successfully treated with etanercept and acitretin

General pustular psoriasis (GPP) is a rare form of psoriasis and is clinically characterized by widespread eruptions of sterile pustules and bright erythematous skin accompanied by periods of fever, chills, rigors, neutrophilia, and elevated serum C-reactive protein.1 Acrodermatitis of Hallopeau, palmoplantar psoriasis pustulosis, and annular pustular psoriasis may be variations of this GPP.2 In 2011, Marrakchi et al3 reported a subgroup of GPP patients with a specific genetic defect: a deficiency of interleukin-36 receptor antagonist (DITRA).

The coexistence of lupus erythematosus panniculitis and subcutaneous panniculitis-like T-cell lymphoma in the same patient

Lupus erythematosus panniculitis (LEP) most commonly presents as multiple deep subcutaneous indurated nodules or erythematous plaques involving the face and proximal extremities.1 Lipoatrophy is another characteristic feature on resolution.2,3 Histopathologically, LEP shows lymphoplasmacytic lobular panniculitis, often with dermal mucin deposition, hyaline fat necrosis, and lymphoid follicles. There may be epidermal vacuolar change and a perivascular and periadnexal lymphocytic infiltrate with prominent plasma cells.

Generalized morphea/eosinophilic fasciitis overlap after epoxy exposure

Generalized morphea is associated with epoxy resin vapors and is characterized by the development of lesions shortly after exposure. Morphea presenting along with eosinophilic fasciitis (EF), or morphea/EF overlap, is rare and an indicator of poor prognosis and resistance to treatment. Here we present a case of generalized morphea/EF overlap linked to epoxy exposure. Our patient received multiple therapies—ultraviolet A1 phototherapy, prednisone, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, and rituximab—none of which led to a significant response.

Lipofibromatosis-like neural tumor: Case report of a unique infantile presentation

A 14-month-old boy presented with a slow-growing, asymptomatic back plaque, which was biopsied and found to have S100 positivity, sparse CD34 staining, and no significant mitotic activity, nuclear pleomorphism, or necrosis; genetic workup found LMNA-NTRK1 gene fusion, overall consistent with lipofibromatosis-like neural tumor (LPF-NT). LPF-NT is rare, with 14 cases previously reported, and our patient is the first report of this diagnosis in infancy. This case report and literature review includes comparison of similar diagnoses including lipofibromatosis, low-grade malignant peripheral nerve sheath tumor, infantile fibrosarcoma, and dermatofibrosarcoma protuberans and serves to aid detection of LPF-NT presenting in pediatric patients by highlighting similarities and differences that should prompt consideration.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: Case report of severe multiorgan involvement to perindopril/amlodipine combination antihypertensive

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening adverse drug reaction with an up to 10% mortality rate. It is characterized by fever, skin eruption, lymphadenopathy, and systemic organ dysfunction. Aromatic anticonvulsants were the first identified culprit medications.1-3 This condition has a prolonged latency period with clinical disease developing up to 2 months after exposure.1,4-6 We report a case of severe DRESS syndrome secondary to a combination of the antihypertensive medications, perindopril and amlodipine.

Vitiligo immune reconstitution inflammatory syndrome (IRIS)—An incidental finding in a tertiary teaching hospital in southeast Nigeria

Skin diseases occur at every stage of HIV infection. They not only act as markers of disease, they may reflect the underlying immune status.1 An estimated 90% of HIV-infected individuals will have at least 1 dermatologic manifestation during the course of disease.2-4 These diseases may be infections, noninfectious inflammatory conditions, or neoplasms.5 Pigmentary abnormalities may occur as a side effect of antiretroviral therapy (ART) itself or from effects of drug treatment of opportunistic infections.

Multiple epidermotropic melanoma metastases developing during BRAF and MEK inhibitor therapy

Since introduction of BRAF and MEK inhibition therapy, there has been a significant improvement in response rates, overall survival, and progression-free disease in melanoma patients.1-3 Combined BRAF and MEK inhibition, compared with BRAF inhibition alone, has shown to delay the emergence of resistance in patients suffering from BRAF V600–mutated advanced melanoma. It has become the standard of care in patients carrying this mutation.4 Several mechanisms of resistance to BRAF and MEK inhibition have been shown.

Random skin biopsy for diagnosis of intravascular large B-cell lymphoma in a patient with hypoxemia and normal lung imaging

Intravascular large B-cell lymphoma (IVLBCL) is a very rare type of non-Hodgkin lymphoma in which tumor cells proliferate within the lumina of small blood vessels, particularly within capillaries, causing clinical symptoms.1 The clinical presentation of IVLBCL differs among geographic areas. For example, Asians more commonly present with fever, hepatosplenomegaly, thrombocytopenia, bone marrow involvement, and hemophagocytic syndrome and only rarely with central nervous system involvement or cutaneous lesions, which are more often seen in western populations.

Acute generalized exanthematous pustulosis simulating Stevens-Johnson syndrome/toxic epidermal necrolysis associated with the use of vismodegib

Basal cell carcinoma (BCC) is a common skin neoplasm that usually has a nonaggressive behavior typically managed with local treatment (eg, surgery, photodynamic treatment, topical agents, or radiation). In some cases, BCC has a much more invasive behavior (locally advanced or metastatic BCC), which may require systemic treatment.1 An abnormal activation of the hedgehog pathway signaling has been linked to the pathogenesis of BCC. Vismodegib is the first-in-class inhibitor of this pathway.1,2 Patients with inoperable or unresectable disease are candidates for this treatment.

Issue Information

Seasonal variation of heavy metals in water, sediment, and highly consumed cultured fish ( Labeo rohita and Labeo bata ) and potential health risk assessment in aquaculture pond of the coal city, Dhanbad (India)

Abstract

The extent of heavy metal pollution and their impact on the various component of urban aquaculture pond (India) were investigated on the basis of seasonal variation. The water, sediment, and fish samples (Labeo rohita and Labeo bata) were collected and analyzed to assess the metal toxicity. In the sediment, geoaccumulation index (I_geo), contamination factor (CF), pollution load index (PLI), and ecological risk index (ERI) were calculated. The estimated daily dietary intake (EDI) for As, Cd, Cr, Mn, Pb, and Zn was estimated in adult and children on the basis an average amount of fish consumed by the Indian people and its associated health hazard with was also assessed in terms of target hazard quotients (THQs). The concentration of metals in all the analyzed samples was found higher during pre-monsoon season. While, in case of fish, L. bata species has higher metal accumulation rate during both the seasons than the L. rohita because of their bottom dweller feeding habit. The order of metals in L. bata muscles is Zn > Mn > Pb > Cr > As > Cd. The I_geo value for Zn (2.66 to 3.68) was found to be highest and followed by Cd (1.65 to 3.52) and Pb (1.52 to 2.55) indicating moderate to highly polluted sediment quality. The values of ERI were significantly high during pre-monsoon period and varied from 319 to 557, representing very high metal contamination. From the human health perspective, present study highlighted that the local inhabitants who rely on this valuable pond for fish consumption are exposed chronically to As and Pb pollution due to higher THQ values, especially from the intake of L. bata.

Metals in Racomitrium lanuginosum from Arctic (SW Spitsbergen, Svalbard archipelago) and alpine (Karkonosze, SW Poland) tundra

Abstract

Arctic-alpine tundra habitats are very vulnerable to the input of relatively small amounts of xenobiotics, and thus their level in such areas must be carefully controlled. Therefore, we collected the terrestrial widespread moss Racomitrium lanuginosum (Hedw.) Brid. in Spitsbergen in the Arctic moss lichen tundra and, for comparison, in the Arctic-alpine tundra in the Karkonosze (SW Poland). Concentrations of the elements Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Na, Ni, Pb, V, and Zn in this species and in the parent rock material were measured. We tested the following hypothesis: R. lanuginosum from Spitsbergen contains lower metal levels than the species from the Karkonosze collected at altitudes influenced by long-range transport from former Black Triangle industry. Principal component and classification analysis (PCCA) ordination revealed that mosses of Spitsbergen were distinguished by a significantly higher Na concentration of marine spray origin and mosses of Karkonosze were distinguished by significantly higher concentrations of Cd, Cr, Cu, Fe, Hg, Li, Mn, Pb, V, and Zn probably from long-range atmospheric transport. The influence of the polar station with a waste incinerator resulted in significantly higher Co, Li, and Ni concentrations in neighbouring mosses in comparison with this species from other sites. This investigation contributes to the use of R. lanuginosum as a bioindicator for metal contamination in Arctic and alpine tundra regions characterised by severe climate habitats with a restricted number of species. This moss enables the control of pollution usually brought solely by long-range atmospheric transport in high mountains as well as in Arctic areas.

Comparison of emerging contaminants in receiving waters downstream of a conventional wastewater treatment plant and a forest-water reuse system

Abstract

Forest-water reuse (FWR) systems treat municipal, industrial, and agricultural wastewaters via land application to forest soils. Previous studies have shown that both large-scale conventional wastewater treatment plants (WWTPs) and FWR systems do not completely remove many contaminants of emerging concern (CECs) before release of treated wastewater. To better characterize CECs and potential for increased implementation of FWR systems, FWR systems need to be directly compared to conventional WWTPs. In this study, both a quantitative, targeted analysis and a nontargeted analysis were utilized to better understand how CECs release to waterways from an FWR system compared to a conventional treatment system. Quantitatively, greater concentrations and total mass load of CECs was exhibited downstream of the conventional WWTP compared to the FWR. Average summed concentrations of 33 targeted CECs downstream of the conventional system were ~ 1000 ng/L and downstream of the FWR were ~ 30 ng/L. From a nontargeted chemical standpoint, more tentatively identified chemicals were present, and at a greater relative abundance, downstream of the conventional system as well. Frequently occurring contaminants included phthalates, pharmaceuticals, and industrial chemicals. These data indicate that FWR systems represent a sustainable wastewater treatment alternative and that emerging contaminant release to waterways was lower at a FWR system than a conventional WWTP.

Cathepsin D contributes to the accumulation of advanced glycation end products during photoaging

Advanced glycation end products (AGEs) are the final products of nonenzymatic glycation of reducing sugars and reactive aldehydes with proteins, lipids and nucleic acids [1]. As AGEs alter the structure and function of proteins, they contribute to the pathogenesis of many diseases, especially diabetes and aging [2]. Skin is the largest organ of human body, and one typical feature of its aging is the accumulation of AGEs [3]. Glycation-associated skin autofluorescence has been found to be correlated with chronological aging in a large number of healthy subjects [4,5].

MITF-M Regulates Melanogenesis in Mouse Melanocytes

The microphthalamia-associated transcription factor (Mitf) gene was first found in descendants of an irradiated male mouse in the 1940s [1]. Using a transgenic insertional mutations at the Mitf locus, the Mitf gene was first cloned by Arnheiter and his colleagues in 1993 [2]. The Mitf gene is conserved in various vertebrate species, including human, rat, mouse, hamster, chicken and quail [3]. Mitf is known to be essential for melanin-bearing pigment cells across species and tissue types. It encodes basic-helix-loop-helix leucine zipper proteins, which are able to form DNA-binding heterodimers with highly homology-related factors.

Home-based contact immunotherapy with diphenylcyclopropenone for alopecia areata is as effective and safe as clinic-based treatment in patients with stable disease: A retrospective study of 40 patients

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Solam Lee, Won-Soo Lee

Crowdsourcing dermatology: DataDerm, big data analytics, and machine learning technology

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Andrew J. Park, Justin M. Ko, Robert A. Swerlick

Table of Contents

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Forehead horizontal primary closure: A retrospective analysis of 25 cases assessing for long-term eyebrow asymmetry

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Logan M. Skelley, Daniel S. Winchester, Randall K. Roenigk

Information for Readers

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

JAAD Case Reports Article List

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Satisfaction with care and likelihood to recommend ratings attributed to dermatology trainees

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Laura E. McDermott, Margaretta Midura, Vassiliki Papagermanos, Joslyn Kirby, Karolyn A. Wanat, Leah T. Belazarian, Cory Dunnick, Jessica S. Mounessa, Stephanie A. Savory, Nidhi Avashia-Khemka, Andrew Strunk, Amit Garg

Journal Based CME Instructions and Information

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Maintenance of Certification: A grandfatherly ethical analysis

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Benjamin K. Stoff, Lionel Bercovitch, Jane M. Grant-Kels

Editorial Board

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

CME examination

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Frontal fibrosing alopecia and cutaneous comorbidities: A potential relationship with rosacea

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Cristina Pindado-Ortega, David Saceda-Corralo, Diego Buendía-Castaño, Pablo Fernández-González, Óscar M. Monero-Arrones, Pablo Fonda-Pascual, Ana R. Rodrigues-Barata, Pedro Jaén-Olasolo, Sergio Vañó-Galván

Answers to CME examination

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Comparison of cyclic and continuous 308-nm excimer laser treatments for vitiligo: A randomized controlled noninferiority trial

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Jae Min Sung, Jung Min Bae, Hee Young Kang

Weight change and risk of onychomycosis: A nationwide cohort study in Korea

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Seong Jun Ha, Kyung Do Han, Yumee Song, Ji Hyun Lee

CME examination

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

Risk of melanoma in patients with multiple myeloma: A Surveillance, Epidemiology, and End Results population-based study

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Timothy W. Chang, Amy L. Weaver, Jerry D. Brewer, Robert A. Kyle, Christian L. Baum

Answers to CME examination

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3

The ethics of medical marijuana in dermatology

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Walter Liszewski, Benjamin K. Stoff, Ronda S. Farah

Merkel cell carcinoma: Current US incidence and projected increases based on changing demographics

Publication date: March 2018
Source:Journal of the American Academy of Dermatology, Volume 78, Issue 3
Author(s): Kelly G. Paulson, Song Youn Park, Natalie A. Vandeven, Kristina Lachance, Hannah Thomas, Aude G. Chapuis, Kelly L. Harms, John A. Thompson, Shailender Bhatia, Andreas Stang, Paul Nghiem
BackgroundMerkel cell carcinoma (MCC) incidence rates are rising and strongly age-associated, relevant for an aging population.ObjectiveDetermine MCC incidence in the United States and project incident cases through the year 2025.MethodsRegistry data were obtained from the SEER-18 Database, containing 6600 MCC cases. Age- and sex-adjusted projections were generated using US census data.ResultsDuring 2000-2013, the number of reported solid cancer cases increased 15%, melanoma cases increased 57%, and MCC cases increased 95%. In 2013, the MCC incidence rate was 0.7 cases/100,000 person-years in the United States, corresponding to 2488 cases/year. MCC incidence increased exponentially with age, from 0.1 to 1.0 to 9.8 (per 100,000 person-years) among age groups 40-44 years, 60-64 years, and ≥85 years, respectively. Due to aging of the Baby Boomer generation, US MCC incident cases are predicted to climb to 2835 cases/year in 2020 and 3284 cases/year in 2025.LimitationsWe assumed that the age-adjusted incidence rate would stabilize, and thus, the number of incident cases we projected might be an underestimate.ConclusionAn aging population is driving brisk increases in the number of new MCC cases in the United States. This growing impact combined with the rapidly evolving therapeutic landscape warrants expanded awareness of MCC diagnosis and management.

Fluorescence quenching of MoS 2 nanosheets/DNA/silicon dot nanoassembly: effective and rapid detection of Hg 2+ ions in aqueous solution

Abstract

Mercury (Hg) contamination of aquatic sites represents a serious risk for human health and the environment. Therefore, effective and rapid monitoring of Hg in aqueous samples is a challenge of timely importance nowadays. In the present study, a rapid and sensitive mercury sensor based on the fluorescence quenching of MoS₂ nanosheets/DNA/silicon dot nanoassembly has been developed for the efficient detection of mercury(II) in aquatic environments. In this process, silicon dots were synthesized through one-step high-temperature calcinations and thermomagnesium reduction method at 900 °C using rice husk as a silicon source, which demonstrates superior photophysical properties and excitation-dependent fluorescence behavior. The interaction between MoS₂ nanosheets/DNA/silicon dot nanoassembly and Hg²⁺ ions was studied using photoluminescence spectroscopy. The addition of Hg²⁺ ions to the assay solution induced the detachment of fluorescent probe from the surface of MoS₂ nanosheets. Thus, the fluorescent probes sustained its fluorescence intensity. The developed sensor was tested on various concentrations of Hg²⁺ ions ranging from 0 to 1000 nM as well as on various metal ions. In addition, MoS₂ nanosheets/DNA/silicon dot nanoassembly fluorescent Hg sensor efficiently detected the presence of Hg²⁺ ions in real-time water samples, which was comparably detected by the conventional atomic absorbance spectrometer (AAS). Overall, our results highlighted the high reliability of the present approach for environmental monitoring of Hg²⁺ ions, if compared to that of the customary method with a lowest detection limit of 0.86 nM.

Larvicidal activity of selected plant extracts and their combination against the mosquito vectors Culex quinquefasciatus and Aedes aegypti

Abstract

In order to develop an environment-friendly botanical mosquito larvicide alternative to the chemical larvicides, extracts were made from the leaves of Hyptis suaveolens, Lantana camara, Nerium oleander, and Tecoma stans with three organic solvents such as methanol (ME), chloroform (CH), and petroleum ether (PE) using a Soxhlet extractor. The plant extracts were screened for larvicidal activity individually and in combination against the larvae of Aedes aegypti and Culex quinquefasciatus as per WHO protocol. Among the extracts, the maximum larvicidal activity was shown by the PE extract of L. camara (LC₅₀ 10.63 mg/L) followed by the PE extract of T. stans (LC₅₀ 19.26 mg/L), ME extract of N. oleander (LC₅₀ 35.82 mg/L), and PE extract of H. suaveolens (LC₅₀ 38.39 mg/L) against Cx. quinquefasciatus. In the case of Ae. aegypti, the PE extract of T. stans showed maximum activity with LC₅₀ value of 55.41 mg/L followed by H. suaveolens (LC₅₀ 64.49 mg/L), PE extract of L. camara (LC₅₀ 74.93 mg/L), and ME extract of N. oleander (LC₅₀ 84.09). A blend of these four extracts resulted in a combination with corresponding LC₅₀ values of 4.32 and 7.19 mg/L against Cx. quinquefasciatus and Ae. aegypti. The predator safety factors were 12.55 and 20.88 for Gambusia affinis with respect to Aedes and Culex larvae for the extract combination. Chemical constituents in extracts were also identified by FT-IR and GC-MS data. The present investigations suggest the possible use of this blend of botanical extracts as an ideal ecofriendly, larvicide against Ae. aegypti and Cx. quinquefasciatus larvae.

Improving photoelectrochemical reduction of Cr(VI) ions by building α-Fe 2 O 3 /TiO 2 electrode

Abstract

Photoelectrochemical process is an environmentally friendly technology and has a wide application in the control of environmental pollutants. Efficient nanophotocatalysts responsive to visible light are still highly attractive. In this work, α-Fe₂O₃/TiO₂ were grown on fluorine doped tin oxide (FTO) substrates by hydrothermal method for photoelectrochemical reduction of Cr(VI). Compared with the separate α-Fe₂O₃ and TiO₂ electrodes, the composite α-Fe₂O₃/TiO₂ electrodes show higher photocurrent density. Under visible light irradiation, 100% removal efficiency of Cr(VI) was obtained after 40 min treatment. The composite α-Fe₂O₃/TiO₂ electrodes showed an enhanced absorbance in visible light region and had good stability to photoelectrochemical reduction of Cr(VI). The role of hole scavengers (citric acid and oxalic acid) and pH values was systematically investigated. This novel intensification approach provides new insight on the application of photoelectrochemical reduction in environmental remediation.

Mediative mechanism of bicarbonate on anaerobic propionate degradation revealed by microbial community and thermodynamics

Abstract

Syntrophic acetogenesis of volatile fatty acids (VFAs) such as propionate and butyrate is considered as the rate-limiting step of anaerobic digestion. Though being extensively researched, the mechanism is not well understood as the main constraint on developing effective solutions to the practical problem. In the present research work, the mediation of methanogenic propionate degradation by exogenous bicarbonate was evaluated, while the mechanism was revealed by microbial community and thermodynamics. It was found that the exogenous bicarbonate not more than 0.10 mol/L acted as a mediative role to enrich syntrophic acetogenic bacteria and decrease the actual Gibbs free energy change (ΔG) of syntrophic acetogenesis reaction, resulted in the increased degradation rate and methane production rate of propionate. The remarkably increased ΔG of methanogenic propionate degradation by the exogenous bicarbonate more than 0.15 mol/L decreased the degradation rate and methane production rate of propionate, though the ΔG of syntrophic acetogenesis reaction was also decreased by the exogenous bicarbonate. This research work provided a control strategy to enhance syntrophic acetogenesis, as well as the methanogenic VFAs degradation.

Role of soil physicochemical properties in quantifying the fate of diuron, hexazinone, and metribuzin

Abstract

The physicochemical properties of soil are fundamental to quantification of the fate of herbicides. Thus, the aim of this research was to evaluate the fate of diuron, hexazinone, and metribuzin in five soils (Clay-1, Clay-2, Loam-1, Loam-2, and Sand), presenting variation in clay content, cation exchange capacity (CEC), pH, and organic carbon (OC). Herbicides radiolabeled with ¹⁴C were applied, and the ¹⁴C–CO₂ released from mineralization was trapped in 0.2 mol L⁻¹ sodium hydroxide solution. The degradation ratio, as well as herbicide-bound residues (non-extractable), transformation products, and residues extractable from soil, was also evaluated. Average ¹⁴C–CO₂ evolution accumulated for diuron mineralization was higher (22.24%) than hexazinone (7.73%) and metribuzin (3.20%). The degradation time half-life (DT50) values for hexazinone correlated with soil OC content. Although no correlation between soil properties and DT50 values was found for metribuzin, the degradation rate and total degree of mineralization were low in sand soil for metribuzin. Regarding diuron, OC content and CEC value appear to be related to mineralization and degradation rate, respectively. Differences in soil properties can influence the persistence and fate of herbicides, affecting their impact on the environment, weed control, and possible effects on subsequent crops.

Rhizospheric effects on atrazine speciation and degradation in laterite soils of Pennisetum alopecuroides (L.) Spreng

Abstract

Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a worldwide-used herbicide and often detected in agricultural soils and groundwater at concentrations above the permitted limit, because of its high mobility, persistence, and massive application. This study applied pot experiments to investigate the atrazine contents and speciation during the phytoremediation process by Pennisetum alopecuroides (L.) Spreng. in laterite soils. From the change of the total atrazine and bioavailable atrazine measured by diffusive gradients in thin film (DGT), P. alopecuroides significantly improved atrazine degradation efficiency from 15.22 to 51.46%, attributing to the increasing bioavailable atrazine in rhizosphere. Only a small amount of atrazine was taken up by P. alopecuroides root and the acropetal translocation from roots to shoots was limited. The atrazine speciation was significantly different between rhizosphere and non-rhizosphere, attributing to the declining pH and organic matters in rhizosphere. The relationship between pH and soil-bound/humus-fixed atrazine illustrated the pH-dependant release of the atrazine from soils and the competition between humus adsorption and uptake by P. alopecuroides. The present study reveals the important roles of soil pH and organic matters in atrazine speciation and availability in laterite soils, and provides new insights in the rhizospheric effects on effective phytoremediation of atrazine.

Effect of spent mushroom substrate as a bulking agent on gaseous emissions and compost quality during pig manure composting

Abstract

The aim of this study was to investigate the gaseous emissions (CH₄, N₂O, and NH₃) and compost quality during the pig manure composting by adding spent mushroom substrate (SMS) as a bulking agent. The control treatment was also studied using corn stalk (CS) as a bulking agent. The experiment was conducted in a pilot scale composting reactor under aerobic condition with the initial C/N ratio of 20. Results showed that bulking agents significantly affected gaseous emissions and compost quality. Using SMS as a bulking agent improved composting efficiency by shortening the time for maturity. SMS increased germination index and humic acid of the final compost (by 13.44 and 41.94%, respectively) compared with CS. Furthermore, composting with SMS as a bulking agent could reduce nitrogen loss, NH₃, and N₂O emissions (by 13.57, 35.56, and 46.48%, respectively) compared with the control. SMS slightly increased CH₄ emission about 1.1 times of the CS. However, a 33.95% decrease in the global warming potential of CH₄ and N₂O was obtained by adding SMS treatment. These results indicate that SMS is a favorable bulking agent for reducing gaseous emissions and increasing compost quality.

Revisiting energy intensity convergence: new evidence from OECD countries

Abstract

In this study, we examine the energy intensity convergence in OECD countries within the context of recent developments in unit root analysis by paying attention to modeling structural shifts. We collect the total primary energy consumption/GDP data of 27 OECD countries during the period 1980–2014. The findings indicate that controlling for shifts plays a crucial role, and different approximations in modeling breaks lead to changes in inferences. In conclusion, we present some policy proposals.

Improved Wound Remodeling Correlates with Modulated TGF-beta Expression in Skin Diabetic Wounds Following Combined Red and Infrared Photobiomodulation Treatments

Abstract

Diabetic wounds are a major cause of morbidity among patients with poorly controlled blood glucose levels. Conventional empirical wound care strategies have shown limited efficacy and there is an urgent need to develop novel therapeutic strategies. Photobiomodulation treatments have shown a positive therapeutic effects in several cell culture and animal models. In this study, we examined wound healing in diabetic rats following treatments with two laser wavelengths, namely red (660nm) and infrared (808nm) individually and in combination as compared to routine wound dressings. Immunostaining for TGF-β expression was performed at various times post-wounding. We noted that the combination of red and infrared laser treatments correlated with decreased TGF-β1 levels at late stages in healing. There was no statistical significance with any treatments at an earlier time point. This study emphasizes the role of appropriate laser treatment protocols in modulating wound healing and remodeling responses.

This article is protected by copyright. All rights reserved.

hsa-let-7b-5p facilitates Mycobacterium tuberculosis survival in THP-1 human macrophages by Fas down regulation

Abstract

Tuberculosis continues to be one of the deadliest infectious disease worldwide. MicroRNAs (miRNAs) are small non-coding entities that play critical role as post-transcriptional regulators and are transcriptionally deregulated upon mycobacterial infection. In this study, we found significant upregulation of hsa-let-7b-5p in Mycobacterium tuberculosis (MTB) infected THP-1 human macrophages. Concomitantly, we detected the reduced level of Fas protein, one of the targets of hsa-let-7b-5p, in MTB infected THP-1 macrophages. Using luciferase assay a direct interaction between hsa-let-7b-5p and the Fas 3'-untranslated region (UTR) was established. Inhibition of hsa-let-7b-5p augmented the apoptosis of THP-1 cells enabling enhanced clearance of MTB. Our findings suggest that hsa-let-7b-5p helps intracellular survival of MTB in THP-1 cells by down-regulating Fas protein level. This highlights hsa-let-7b-5p as a potential therapeutic target for tuberculosis treatment.

Variable response of nirK and nirS containing denitrifier communities to long term pH manipulation and cultivation

Abstract

Denitrification is a key process responsible for the majority of soil nitrous oxide (N₂O) emissions but the influences of pH and cultivation on the soil denitrifier community remain poorly understood. We hypothesised that the abundance and community structure of the total bacterial community and bacterial denitrifiers would be pH sensitive and that nirK and nirS containing denitrifiers would differ in their responses to change in pH and cultivation. We investigated the effect of long-term pH adjusted soils (ranging from pH 4.2 to pH 6.6) under different lengths of grass cultivation (one, two and three years of ley grass) on the general bacterial and denitrifier functional communities using 16S rRNA, nirK and nirS genes as markers. Denitrifier abundance increased with pH, and at pH below 4.7 there was a greater loss in nirS abundance per unit drop in pH than soils above this threshold pH. All community structures responded to changes in soil pH whilst cultivation only influenced the community structure of nirK. These differences in denitrifier responses highlight the importance of considering both nirK and nirS gene markers for estimating denitrifier activity. Identifying such thresholds in response of the microbial community to changes in pH is essential to understanding impacts of management or environmental change.

The value of knowing how

Abstract

Know-how has a distinctive, non-instrumental value that a mere reliable ability lacks. Some, including Bengson and Moffett (in: Bengson, Moffett (eds) Knowing how, Oxford University Press, Oxford, pp 161–195, 2011) and Carter and Pritchard (Australas J Philos 93(4):799–816, 2015b) have cited a close relation between knowhow and cognitive achievement, and it is tempting to think that the value of know-how rests in that relation. That's not so, however. The value of know-how lies in its relation to the fundamental value of autonomy.

Beauty, odds, and credence

Abstract

This paper considers fair betting odds for certain bets that might be placed in the situation discussed in the so-called Sleeping Beauty Problem. This paper examines what Thirders, Halfers, and Double Halfers must say about the odds as determined by various decision theoretic approaches and argues that Thirders and Halfers have difficulties formulating plausible and coherent positions concerning the relevant betting odds. Double Halfers do not face this problem and that is an important consideration in favor of Double Halfers.

A Green Method to Determine VUV (185 nm) Fluence Rate Based on Hydrogen Peroxide Production in Aqueous Solution

Abstract

A mini-fluidic vacuum ultraviolet/ultraviolet (VUV/UV) photoreaction system (MVPS) was developed in our previous study. Based on the MVPS, a green method to determine VUV fluence rate has been developed using the production rate of H₂O₂ when water is exposed to 185 nm VUV. The H₂O₂ production followed pseudo-zero-order reaction kinetics well over the first 10 min of VUV/UV exposure. This new method was well calibrated with a standard cis-cyclooctene cis-trans photoisomerization actinometer as recommended by the International Union of Pure and Applied Chemistry. The apparent quantum yield for H₂O₂ production by 185 nm VUV irradiation of water was determined to be 0.024 ± 0.002. As the solution pH increased from 5.0 to 8.0, the H₂O₂ production rate decreased from 0.83 to 0.40 μM min^–1. Dissolved oxygen had a negligible influence on the H₂O₂ production. This study proposes a novel VUV fluence rate determination method with advantages of non-toxicity, low detection limits, low costs and convenience, and it can be used as a good alternative to traditional actinometers.

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Preconditioning With Low Level Laser Irradiation Enhances the Therapeutic Potential of Human Adipose-derived Stem Cells in a Mouse Model of Photoaged Skin

Abstract

The present study was conducted to explore the therapeutic potential of human adipose-derived stem cells (ADSCs) irradiated with a low level laser (LLL). Cultured ADSCs were treated with 650-nm GaAlAs laser irradiation at 2, 4, and 8 J/cm². Cell proliferation was quantified by MTT assays, cytokine secretion was determined by enzyme-linked immunosorbent assays, and adipogenic differentiation was examined by oil red O staining. Additionally, the expression profiles of putative ADSC surface markers were analyzed by quantitative real-time PCR. In addition, a mouse photoaged skin model was established by UVB irradiation. Effects of GaAlAs-laser-treated ADSCs on thicknesses of the epidermis and dermis were analyzed by hematoxylin and eosin staining. The results showed that GaAlAs laser treatment of cells at a radiant exposure of 4 J/cm² enhanced ADSC proliferation and adipogenic differentiation, and increased secretion of growth factors. Furthermore, GaAlAs laser irradiation upregulated the expression of putative ADSC surface markers. In the mouse model of photoaged skin, ADSCs treated with GaAlAs laser irradiation had a markedly decreased the epidermal thickness and increased dermal thickness of photoaged mouse skin. Our data indicate that LLL irradiation is an effective biostimulator of ADSCs and might enhance the therapeutic potential of ADSCs for clinical use.

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Human papillomavirus infection and lichen sclerosus: coincidence or link?

When trichoscopy enlightens clinics: more about discoid lupus

Composition as pattern

Abstract

I argue for patternism, a new answer to the question of when some objects compose a whole. None of the standard principles of composition comfortably capture our natural judgments, such as that my cat exists and my table exists, but there is nothing wholly composed of them. Patternism holds, very roughly, that some things compose a whole whenever together they form a "real pattern". Plausibly we are inclined to acknowledge the existence of my cat and my table but not of their fusion, because the first two have a kind of internal organizational coherence that their putative fusion lacks. Kolmogorov complexity theory supplies the needed rigorous sense of "internal organizational coherence".

Ecological and human health risks arising from exposure to metals in urban soils under different land use in Nigeria

Abstract

The concentrations of eight metals (Cd, Pb, Cr, Ni, Cu, Mn, Zn and Fe) were measured in soils under different land use in an urban environment of the Niger Delta in Nigeria. The aim was to provide information on the potential ecological and human health risks associated with human exposure to metals in these soils. The potential ecological risk due to metals in soils of these land use types falls in the range of low to moderate ecological risk with a significant contribution from Cd. The severity of the individual metals to ecological risk in these land use types followed the order Cd > Pb > Zn > Cu > Ni > Cr > Mn. The non-carcinogenic risk, expressed in terms of the hazard index (HI), arising through exposure to metals through oral, dermal and inhalation pathways, was greater than 1 for children in the majority of the land use types and less than 1 for adults for all land use types. This indicated that there are considerable non-cancer risks arising from childhood exposure to metals in soils of these land use types. The cancer risk values were within acceptable threshold values indicating a negligible cancer risk for both children and adults exposed to metals in these urban soils.

Impact of hand eczema on quality of life: metropolitan versus non-metropolitan areas

Summary

Background

An inverse relationship between disease severity and health-related quality of life (HR-QoL) in patients with hand eczema is well established, but modifying effects of demographic variables have been less well studied.

Objective

To identify the influence of metropolitan versus non-metropolitan residence on the relationship between disease severity and HR-QoL in patients with occupational hand eczema.

Methods

The city of Copenhagen and the rest of Zealand were defined as metropolitan and non-metropolitan areas, respectively. Participants were 773 persons with occupational hand eczema. A questionnaire on the severity of hand eczema and HR-QoL was sent to all participants.

Results

The odds for reporting moderate to high severity of occupational hand eczema were significantly lower in the metropolitan population than in the non-metropolitan population [odds ratio (OR): 0.42; 95%CI: 0.23–0.75], whereas low dermatology-related quality of life was more prevalent in metropolitan than in non-metropolitan patients (OR: 1.31; 95%CI: 0.83–2.05), indicating that hand eczema had a more pronounced negative effect in metropolitan patients, in spite of less severe eczema.

Conclusion

Our data indicate that area of residence has a modifying effect on the relationship between disease severity and HR-QoL, with a more negative impact on HR-QoL in metropolitan than in non-metropolitan areas. This information is important with respect to fully appreciating the burden of occupational hand eczema.

The CBTRUS story: providing accurate population-based statistics on brain and other central nervous system tumors for everyone

The Central Brain Tumor Registry of the United States (CBTRUS) was established to provide descriptive statistical data on all primary brain tumors. The following editorial describes some of the historical events that led to its establishment and its current role as the recognized "go-to" resource for researchers; clinicians and treatment facilities; federal and state agencies; manufacturers of medical drugs and devices; and organizations that provide education, emotional support, and guidance for brain tumor patients and their caregivers.

Highlights from the Literature

Corrigendum

Corrigendum to Beier et al. Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07). Neuro Oncol (doi: https://doi.org/10.1093/neuonc/nox155) first published online 21 August 2017

Forthcoming Meetings

Simultaneous care in neuro-oncology

See the article by Philip et al on pp. 391–399.

A new practical and versatile mouse model of proneural glioblastoma

See the article by Rahme et al. on pp. 332–342.

Challenges of developing small-molecule kinase inhibitors for brain tumors and the need for emphasis on free drug levels

Abstract

Despite biological rationale and significant clinical study, the pursuit of small-molecule kinase inhibitors for the treatment of brain cancers has had very limited success. This Advance-in-Brief discusses the need for drugs to achieve free brain penetration to engage their targets where CNS tumors reside. This need to achieve free, as opposed to total, drug concentrations in the brain may be a contributing factor to why so many small-molecule kinase inhibitors have not realized success in the neuro-oncology setting. For kinase targets of interest for brain cancer, either the vast majority of small-molecule inhibitors have data suggesting that free brain penetration would be limited or there are inadequate data to suggest that free brain penetration could be expected. Therefore, kinase targets of interest in the treatment of brain cancers may be inadequately assessed due to a lack of freely brain-penetrant inhibitors available for clinical study. Encouraging recent drug discovery efforts that focused on achieving free brain penetration for cancers in the CNS are highlighted. Still, further efforts are needed to enable thorough clinical evaluation of biological hypotheses.

Visual and semiquantitative 11C-methionine PET: an independent prognostic factor for survival of newly diagnosed and treatment-naïve gliomas

Abstract

Background

Few data exist regarding the prognostic value of L-[S-methyl-¹¹C]methionine (MET) PET for treatment-naïve gliomas.

Methods

A total of 160 glioma patients (89 men, 71 women; mean age: 45, range 18–84 y) underwent a MET PET prior to any therapy. The PET scans were evaluated visually and semiquantitatively by tumor-to-background (T/N) ratio thresholds chosen by analysis of receiver operating characteristics. Additionally, isocitrate dehydrogenase 1–R132H (IDH1-R132H) immunohistochemistry was performed. Survival analysis was done using Kaplan–Meier estimates and the Cox proportional hazards model.

Results

Significantly shorter mean survival times (7.2 vs 8.6 y; P = 0.024) were seen in patients with amino acid avid gliomas (n = 137) compared with visually negative tumors (n = 33) in MET PET. T/N ratio thresholds of 2.1 and 3.5 were significantly associated with survival (10.3 vs 7 vs 4.3 y; P < 0.001). Mean survival differed significantly using the median T/N ratio of 2.4 as cutoff, independent of histopathology (P < 0.01; mean survival: 10.2 ± 0.8 y vs 5.5 ± 0.6 y). In the subgroup of 142 glioma patients characterized by IDH1-R132H status, METT/N ratio demonstrated a significant prognostic impact in IDH1-R132H wildtype astrocytomas and glioblastoma (P = 0.001). Additionally, multivariate testing revealed semiquantitative MET PET as an independent prognostic parameter for treatment-naïve glioma patients without (P = 0.031) and with IDH1-R132H characterization of gliomas (P = 0.024; odds ratio 1.57).

Conclusion

This retrospective analysis demonstrates the value of MET PET as a prognostic parameter on survival in treatment-naïve glioma patients.

Metabolic heterogeneity and plasticity of glioma stem cells in a mouse glioblastoma model

Abstract

Background

Glioblastomas have been shown to rely on glycolysis as an energy source. However, recent evidence suggests that at least a subset of glioma cells with stem cell–like properties can thrive on oxidative phosphorylation. It remains unclear whether both metabolic phenotypes support tumor propagation, if they are independent, and how stable they are. The present study investigated these questions with the use of isogenic murine glioma stem cells (GSCs).

Methods

GSCs were established from tumors formed by Ink4a/Arf–null, H-Ras^V12-expressing glioma-initiating cells that differed in extracellular acidification potential. Metabolic characteristics of GSCs were determined by measurement of glucose, oxygen, and glutamine uptake, ATP content, and lactate production. Effects of metabolic inhibitors and changes in oxygen or nutrient availability on lactate production and tumorsphere growth were also determined.

Results

GSCs were found either to consume more glucose and produce more lactate or to consume more oxygen and maintain a higher ATP content depending on the metabolic characteristics of the tumor cells of origin. The latter, mitochondrial-type GSCs increased lactate production after treatment with the oxidative phosphorylation inhibitor oligomycin or phenformin. Exposure to hypoxia also increased lactate production and expression of glycolysis-related enzymes and metabolites in mitochondrial-type GSCs in a reversible manner.

Conclusions

Both glycolytic and mitochondrial-type energy production can sustain tumor propagation by isogenic GSCs. Whereas both phenotypes can be independent and stable, cells that rely on oxidative phosphorylation can also switch to a more glycolytic phenotype in response to metabolic stress, suggesting that plasticity is a further characteristic of GSC metabolism.

Long-term exposure to ambient air pollution and incidence of brain tumor: the European Study of Cohorts for Air Pollution Effects (ESCAPE)

Abstract

Background

Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent.

Methods

In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM_2.5, PM₁₀, and PM_coarse), PM_2.5 absorbance, nitrogen oxides (NO₂ and NO_x) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.

Results

Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM_2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89–3.14 per 10^–5/m³), and weak positive or null associations with the other pollutants. Hazard ratio for PM_2.5 absorbance (1.01; 0.38–2.71 per 10^–5/m³) and all other pollutants were lower for nonmalignant than for malignant brain tumors.

Conclusion

We found suggestive evidence of an association between long-term exposure to PM_2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.

Loss of host-derived osteopontin creates a glioblastoma-promoting microenvironment

Abstract

Background

Microglia and periphery-derived monocytes infiltrate human and mouse glioblastoma and their density is positively correlated with malignancy. Using microarray and RNA sequencing, we have previously shown that glioblastoma-associated microglia/monocytes (GAMs) express osteopontin/SPP1.

Methods

We used quantitative reverse transcriptase PCR, immunofluorescence stainings, western blot, and flow cytometry to identify the various sources of osteopontin (OPN) expression in human and mouse glioblastoma. We implanted wild type GL261 glioblastoma cells, which do not express significant levels of OPN, into wild type and OPN^−/− mice to investigate the role of microenvironment-derived OPN on glioblastoma progression.

Results

Our data indicate that GAMs are the predominant source of OPN in both human and mouse glioblastoma and express only the secreted form of OPN. Loss of microenvironment-derived OPN enhanced tumor progression. Staining by Ki67 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling showed no difference in overall cell proliferation but a decreased apoptosis rate in tumors in OPN^−/− mice. CD31 staining showed a significantly decreased number of microvessels in tumors in OPN^−/− mice, accompanied by reduced coverage of vessels with platelet derived growth factor receptor β⁺ pericytes. Flow cytometry analysis revealed a significant increase of CD11b⁺/CD45^low microglia but not of CD11b⁺/CD45^high macrophages/monocytes in tumors in OPN^−/− mice. Sorted CD11b⁺ cells from wild type and OPN^−/− naïve brains and tumors did not show a significant difference in the expression pattern of activation marker genes.

Conclusion

Our results show that in tested human and mouse glioblastoma samples, OPN is predominantly expressed and secreted by GAMs and that, in contrast to OPN expression in the tumor cells per se, loss of stroma-derived OPN creates a glioblastoma-promoting microenvironment.

Molecular differences in IDH wildtype glioblastoma according to MGMT promoter methylation

Abstract

Background

O⁶-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive biomarker in glioblastoma. We investigated whether this marker furthermore defines a molecularly distinct tumor subtype with clinically different outcome.

Methods

We analyzed copy number variation (CNV) and methylation profiles of 1095 primary and 92 progressive isocitrate dehydrogenase wildtype glioblastomas, including paired samples from 49 patients. DNA mutation data from 182 glioblastoma samples of The Cancer Genome Atlas (TCGA) and RNA expression from 107 TCGA and 55 Chinese Glioma Genome Atlas samples were analyzed.

Results

Among untreated glioblastomas, MGMT promoter methylated (mMGMT) and unmethylated (uMGMT) tumors did not show different CNV or specific gene mutations, but a higher mutation count in mMGMT tumors. We identified 3 methylation clusters. Cluster 1 showed the highest average methylation and was enriched for mMGMT tumors. Seventeen genes including gastrulation brain homeobox 2 (GBX2) were found to be hypermethylated and downregulated on the mRNA level in mMGMT tumors. In progressive glioblastomas, platelet derived growth factor receptor alpha (PDGFRA) and GLI2 amplifications were enriched in mMGMT tumors. Methylated MGMT tumors gain PDGFRA amplification of PDGFRA, whereas uMGMT tumors with amplified PDGFRA frequently lose this amplification upon progression. Glioblastoma patients surviving <6 months and with mMGMT harbored less frequent epidermal growth factor receptor (EGFR) amplifications, more frequent TP53 mutations, and a higher tumor necrosis factor–nuclear factor-kappaB (TNF-NFκB) pathway activation compared with patients surviving >12 months.

Conclusions

MGMT promoter methylation status does not define a molecularly distinct glioblastoma subpopulation among untreated tumors. Progressive mMGMT glioblastomas and mMGMT tumors of patients with short survival tend to have more unfavorable molecular profiles.

Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)

Abstract

Background

Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy.

Methods

The NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy.

Results

Thirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock.

Conclusions

Radio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma.

Mesenchymal stem cells as natural biofactories for exosomes carrying miR-124a in the treatment of gliomas

Abstract

Background

MicroRNAs (miRs) are promising new therapeutics for glioblastoma. However, which miRs are most effective against glioblastomas and how these miRs should be delivered are major unanswered problems.

Methods

To identify potent antiglioma miRs, we selected 8 miRs based on a literature search and screened them against a panel of glioma stem cell (GSC) lines, representing all of the glioblastoma subtypes defined by The Cancer Genome Atlas. To address delivery, we tested the hypothesis that ex vivo cultured bone marrow–derived mesenchymal stem cells (MSCs) can package miRs into exosomes and that these engineered exosomes can systemically deliver antiglioma miRs to glioblastomas.

Results

Of the screened miRs, we identified miR-124a as the most effective antiglioma agent against GSCs. We then transduced MSCs with lentivirus vectors containing miR-124a and isolated vesicles from the medium. Electron microscopy, western blotting, and Nanosight proved that the isolated vesicles were exosomes. Quantitative PCR documented that these exosomes contained high levels of miR-124a, which was not present in control exosomes. In vitro treatment of GSCs with exosomes containing miR-124a (Exo-miR124) resulted in a significant reduction in viability and clonogenicity of GSCs compared with controls. In vivo treatment of mice harboring intracranial GSC267 with systemically delivered Exo-miR124 resulted in 50% of animals living long term. No evidence of tumor was present on histological analysis of the survivors. Mechanistic studies showed that miR-124a acts by silencing Forkhead box (FOX)A2, resulting in aberrant intracellular lipid accumulation.

Conclusion

MSCs can be used as natural biofactories to produce Exo-miR124, which is an effective antiglioma agent worthy of further clinical evaluation.

A proposed framework of supportive and palliative care for people with high-grade glioma

Abstract

Background

Patients with malignant high-grade glioma (HGG) have significant supportive and palliative care needs, yet few tailored guidelines exist to inform practice. This study sought to develop an HGG framework of supportive and palliative care informed by needs reported by patients, families, and health care professionals (HCPs).

Methods

This study integrates a mixed-methods research program involving: (i) exploring experiences through systematic literature review and qualitative study (10 patients, 23 carers, and 36 HCPs); and (ii) an epidemiological cohort study (N = 1821) describing care of cases of HGG in Victoria, Australia using linked hospital datasets. Recommendations based on these studies were developed by a multidisciplinary advisory committee for a framework of supportive and palliative care based on the findings of (i) and (ii).

Results

Key principles guiding framework development were that care: (i) aligns with patient/family caregiver needs according to illness transition points; (ii) involves continuous monitoring of patient/family caregiver needs; (iii) be proactive in response to anticipated concerns; (iv) includes routine bereavement support; and (v) involves appropriate partnership with patients/families. Framework components and resulting activities designed to address unmet needs were enacted at illness transition points and included coordination, repeated assessment, staged information provision according to the illness transition, proactive responses and referral systems, and specific regular inquiry of patients' and family caregivers' concerns.

Conclusion

This evidence-based, collaborative framework of supportive and palliative care provides an approach for patients with HGG that is responsive, relevant, and sustainable. This conceptual framework requires evaluation in robust clinical trials.

Clinical characteristics associated with postoperative seizure control in adult low-grade gliomas: a systematic review and meta-analysis

Abstract

Background

Epilepsy is the most common symptom in patients with supratentorial low-grade gliomas (LGGs), which adversely affects the patient's quality of life. Poor seizure control with anti-epileptic therapy is an indication for surgery in these patients. Recent studies have sought to identify predictors of postoperative seizure control after surgical resection of LGG; gross total resection was shown to be a significant predictor in this respect. However, the prognostic value of other factors is not clear.

Methods

We performed a systematic review and meta-analysis of 23 studies with a combined study population of 2641 patients with LGG, in order to identify potential factors associated with favorable postoperative seizure control. Data were extracted on age and sex of patient, tumor location, tumor histology, type of seizure, seizure duration, extent of resection, and imaging characteristics.

Results

Patients ≥45 years of age achieved better postoperative seizure control (risk ratio [RR], 0.89; 95% CI, 0.81–0.99). Focal seizures were associated with poor seizure control (RR, 1.32; 95% CI, 1.18–1.49) compared with generalized seizures (RR, 0.77; 95% CI, 0.68–0.87). Prolonged history of seizures (≥1 y) had a negative impact on postoperative seizure control (RR, 1.22; 95% CI, 1.10–1.34). Gross total resection was superior to subtotal resection with respect to postoperative seizure control (RR, 0.68; 95% CI, 0.63–0.73).

Conclusions

This systematic review and meta-analysis identified predictors of postoperative seizure control in patients undergoing surgical resection of LGGs. Our results provide a reference for clinical treatment of LGG-related epilepsy.

A recombinant lentiviral PDGF-driven mouse model of proneural glioblastoma

Abstract

Background

Mouse models of glioblastoma (GBM), the most aggressive primary brain tumor, are critical for understanding GBM pathology and can contribute to the preclinical evaluation of therapeutic agents. Platelet-derived growth factor (PDGF) signaling has been implicated in the development and pathogenesis of GBM, specifically the proneural subtype. Although multiple mouse models of PDGF-driven glioma have been described, they require transgenic mice engineered to activate PDGF signaling and/or impair tumor suppressor genes and typically represent lower-grade glioma.

Methods

We designed recombinant lentiviruses expressing both PDGFB and a short hairpin RNA targeting Cdkn2a to induce gliomagenesis following stereotactic injection into the dentate gyrus of adult immunocompetent mice. We engineered these viruses to coexpress CreERT2 with PDGFB, allowing for deletion of floxed genes specifically in transduced cells, and designed another version of this recombinant lentivirus in which enhanced green fluorescent protein was coexpressed with PDGFB and CreERT2 to visualize transduced cells.

Results

The dentate gyrus of injected mice showed hypercellularity one week post-injection and subsequently developed bona fide tumors with the pathologic hallmarks of GBM leading to a median survival of 77 days post-injection. Transcriptomic analysis of these tumors revealed a proneural gene expression signature.

Conclusion

Informed by the genetic alterations observed in human GBM, we engineered a novel mouse model of proneural GBM. While reflecting many of the advantages of transgenic mice, this model allows for the facile in vivo testing of gene function in tumor cells and makes possible the rapid production of large numbers of immunocompetent tumor-bearing mice for preclinical testing of therapeutics.

miR miR on the wall, who’s the most malignant medulloblastoma miR of them all?

Abstract

microRNAs (miRNAs) have wide-ranging effects on large-scale gene regulation. As such, they play a vital role in dictating normal development, and their aberrant expression has been implicated in cancer. There has been a large body of research on the role of miRNAs in medulloblastoma, the most common malignant brain tumor of childhood. The identification of the 4 molecular subgroups with distinct biological, genetic, and transcriptional features has revolutionized the field of medulloblastoma research over the past 5 years. Despite this, the growing body of research on miRNAs in medulloblastoma has largely focused on the clinical entity of a single disease rather than the molecular subgroups. This review begins by highlighting the role of miRNAs in development and progresses to explore their myriad of implications in cancer. Medulloblastoma is characterized by increased proliferation, inhibition of apoptosis, and maintenance of stemness programs—features that are inadvertently regulated by altered expression patterns in miRNAs. This review aims to contextualize the large body of work on miRNAs within the framework of medulloblastoma subgroups. The goal of this review is to stimulate new areas of research, including potential therapeutics, within a rapidly growing field.

Title Page

Table of Contents

CME Overview

Dupilumab: A review of its use in the treatment of atopic dermatitis

Atopic dermatitis (AD) is a chronic, pruritic immune-mediated inflammatory dermatosis characterized by a T helper 2 (Th2) immune response phenotype and may be associated with systemic inflammation. Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4α subunit. Blockade of IL-4/13 is effective in reducing Th2 response. Dupilumab has recently been approved in the United States and Europe for the treatment of adult patients with moderate-to-severe AD.

Editorial Board

Atopic Dermatitis in Diverse Racial and Ethnic Groups – Variations in Epidemiology, Genetics, Clinical Presentation, and Treatment

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects diverse ethnic groups with varying prevalence. Despite a predominance of studies in individuals of European ancestry, AD has been found to occur more frequently in Asian and black individuals than whites. Therefore, an understanding of the unique clinical features of AD in diverse ethnic groups, as well as the differences in genetic polymorphisms that influence susceptibility to AD and response to current therapies, is paramount for management of an increasingly diverse patient population. In this article, we review key nuances in the epidemiology, pathophysiology, clinical presentation, and treatment of AD in non-white ethnic groups, which are largely under-appreciated in the literature. We highlight the need for studies evaluating the tissue molecular and cellular phenotypes of AD in non-white patients, as well as greater inclusion of minority groups in clinical trials, in order to develop targeted treatments for a multi-ethnic population.

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